Cancer is one of the top two causes of death throughout the world. Many cancer patients die from the serious side effects of chemotherapy or from a relapse after the treatment. The serious side effects are largely due to the destruction of normal cells. The immune system and normal organ functions can be compromised by these treatments.
Cancer therapies have often been based on drugs or surgery or both. For many cancers, surgical treatments may be unsuccessful. Chemotherapy has major drawbacks in that it causes damage to healthy cells and it leads to drug-resistant cancer cells becoming the dominant species. Radiation therapy often has serious side effects because radiation must pass through overlaying tissues. Photon therapy is largely limited to tumors near the skin surfaces.
The chemical approach is based on drugs that are toxic to malignant tumor cells. Unfortunately, most cancer drugs, especially chemotherapy drugs, are also harmful to normal cells and can distinguish little between cancer cells and normal cells. Both “passive” tumor targeting, which utilizes tumor-selective enhanced permeability, and “active” tumor targeting, which is based on the specific interactions between drugs and cancer cell markers, have been used to reduce side effects. Nevertheless, the side effects have not been eliminated, and the targeting drugs are typically costly. Most cancers are highly heterogeneous; an estimated number of more than 100 different types of cells can co-exist in one tumor. When a specific drug is used, some specific cancer cells with resistance to that drug may survive while other cancer cells are killed. These drug-resistant cells then replicate and become the dominant type of cells in the tumor, rendering the drug useless in treating that tumor. Thus, chemotherapy can have a high failure rate due to drug resistance.
Radiation therapy is a physical method of cancer treatment that may utilize ionizing radiation from electromagnetic waves, such as gamma rays or x-rays, particles such as electrons, protons, neutrons and alpha particles, and non-ionizing radiation such as light, microwaves, and radio waves. These forms of radiation have different energy levels and can penetrate cells to varying extents. The ionizing radiation is intended to be directed only at the tumor. However, because the radiation is difficult to focus, it can also affect the normal tissues as it passes through the patient's body. Thus, normal cells are affected by ionizing radiation, which causes undesirable side effects. Ionizing radiation itself may cause DNA mutation in normal cells, causing them to become cancerous.
Light as non-ionizing radiation is used as a photodynamic therapy for tumors. Photodynamic therapy transforms oxygen into reactive oxygen species (ROS) inside the cells and subsequently induces cell apoptosis and necrosis. One of the major limitations of photodynamic methods is that solid tumor cells become oxygen deficient. Hypoxic cells are known to be resistant to photodynamic therapy. Other drawbacks of photodynamic therapy are limited ability to penetrate the body and the requirement of toxic dyes.
Other non-ionizing radiation therapies are largely based on the hyperthermia of tumors caused by radio waves and ultrasound. Clinical examinations indicate that malignant cells subjected to hyperthermia killing are more sensitive than their normal counterparts.
Ultrasound and radiofrequency waves may achieve non-intrusive therapy or imaging by penetrating deep inside the human body without harming the tissues. The disadvantage of the therapies based on radio-frequency electromagnetic waves is the need for high-power radiofrequency which can lead to serious side effects.
Unlike radiofrequency, ultrasound (US) can be easily focused onto a small, well-defined area of interest. Focused ultrasound is a non-intrusive technology that can be used to generate local hyperthermia. Focused ultrasound can be used for tumor ablation. However, while a high-intensity focused ultrasound (HIFU) can ablate tumors deep within the body without harming the overlying skin or adjacent connective tissues, normal cells near the tumor region are killed by the intense ultrasound.
There is a continuing need for methods to improve outcomes and reduce side effects in cancer treatment. There is also a need for compositions, formulations, materials and methods to improve outcomes and reduce side effects in treatment of cancers. More particularly, there is a need for methods that reduce the level of ionizing radiation in cancer treatment. There is also a need for methods that reduce the destruction of normal cells in cancer treatment. There is a further need for methods in cancer treatment that avoid drug-resistant cancer cells becoming dominant. There is also a need for methods in cancer treatment that avoid development of drug-resistant cancer cells.